Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men

Authors

Clara E. Cho, Utah State UniversityFollow
Niklas D. J. Aardema, Utah State UniversityFollow
Madison L. Bunnell, Utah State UniversityFollow
Deanna P. Larson, Utah State UniversityFollow
Sheryl Aguilar, Utah State UniversityFollow
Janet R. Bergeson, Utah State UniversityFollow
Olga V. Malysheva, Cornell University
Marie A. Caudill, Cornell University
Machael Lefevre, Utah State UniversityFollow

Document Type

Article

Journal/Book Title/Conference

Nutrients

Volume

12

Issue

8

Publisher

M D P I AG

Publication Date

7-25-2020

First Page

1

Last Page

20

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Abstract

Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.

Recommended Citation

Cho, C.E.; Aardema, N.D.J.; Bunnell, M.L.; Larson, D.P.; Aguilar, S.S.; Bergeson, J.R.; Malysheva, O.V.; Caudill, M.A.; Lefevre, M. Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men. Nutrients 2020, 12, 2220. https://doi.org/10.3390/nu12082220